Ovarian cancers tend to be more aggressive in older women due to a combination of biological, molecular, and clinical factors that influence tumor behavior and the body’s response to cancer as age advances. Several key reasons explain why ovarian cancers, particularly the most common types like high-grade serous carcinoma, show increased aggressiveness in older women.
First, the biology of ovarian cancer itself changes with age. High-grade serous carcinoma, which accounts for about 70% of ovarian cancers, is more frequently diagnosed in women over 60. This cancer type is characterized by cells that look very abnormal under the microscope and grow rapidly. By the time symptoms appear, the cancer often has already spread beyond the ovary, making it harder to treat effectively. The vague and nonspecific symptoms such as abdominal bloating, pelvic pain, and changes in bowel habits contribute to delayed diagnosis, which is more common in older women who may attribute these symptoms to other age-related conditions. This delay allows the cancer to progress to advanced stages, increasing its aggressiveness and reducing treatment success.
At the molecular level, older women’s ovarian tumors often exhibit changes that promote immune evasion and tumor progression. For example, the expression of PD-L1, a protein that helps cancer cells hide from the immune system, is more common in advanced ovarian cancers. PD-L1 positivity is associated with higher tumor grade, distant metastases, and increased recurrence risk. This immune evasion mechanism allows tumors in older women to grow unchecked by the body’s natural defenses, contributing to their aggressive nature. Additionally, markers linked to cancer stem cells, such as CD44, have been found in ovarian tumors and are associated with recurrence and resistance to therapy. These molecular features tend to be more pronounced in tumors from older patients, compounding the difficulty of controlling the disease.
Another factor is the aging immune system itself. As women age, their immune surveillance weakens, meaning the body is less capable of detecting and destroying emerging cancer cells. This immunosenescence reduces the effectiveness of immune responses against ovarian tumors, allowing them to grow more aggressively. The combination of tumor immune evasion strategies and a declining immune system creates a perfect storm for aggressive cancer progression in older women.
Furthermore, older women often have other health conditions and reduced physiological reserves, which can limit the intensity and types of treatments they can safely receive. This can result in less aggressive therapy or delays in treatment, giving the cancer more opportunity to advance. The biology of the tumor may also be inherently more resistant to chemotherapy in older patients, although high-grade serous carcinoma remains one of the more chemotherapy-responsive ovarian cancers.
Genetic factors also play a role. While inherited mutations like BRCA1 and BRCA2 increase ovarian cancer risk at younger ages, sporadic mutations accumulate over time in ovarian cells, leading to more aggressive tumor types in older women. The accumulation of DNA damage and epigenetic changes with age can drive the development of high-grade, fast-growing tumors.
In summary, ovarian cancers are more aggressive in older women because these cancers are often diagnosed late due to vague symptoms, have molecular features that promote immune evasion and recurrence, arise in the context of a weakened immune system, and may be less amenable to aggressive treatment due to age-related health factors. The interplay of these biological and clinical factors results in ovarian cancer that grows faster, spreads earlier, and recurs more frequently in older women compared to younger patients.
